Journal of Cancer Research and Clinical Oncology https://doi.org/10.1007/s00432-017-2544-x

ORIGINAL ARTICLE – CLINICAL ONCOLOGY

Head and neck rhabdomyosarcoma in children: a 20-year retrospective study at a tertiary referral center Sophia Marie Häußler1 · Carmen Stromberger2 · Heidi Olze1,3 · Georg Seifert4 · Steffen Knopke1 · Arne Böttcher5 Received: 25 September 2017 / Accepted: 7 November 2017 © Springer-Verlag GmbH Germany, part of Springer Nature 2017

Abstract Objective  The purpose of this study was to assess rhabdomyosarcomas (RMS) of the head and neck in pediatric patients with regard to clinical presentation, treatment, and survival. Methods  Data were retrospectively obtained from patient charts with regard to RMS of the head and neck diagnosed between 1996 and 2016 at a tertiary referral center. Clinical course, treatment modalities, and side effects were analyzed. Survival analysis was carried out using the Kaplan–Meier method. Results  Twenty-eight patients (17 male, 11 female) with a mean age at diagnosis of 6.8 ± 5.0 years have been included. Fourteen patients (50%) presented with painless swelling in the head and neck region and nine patients (32.1%) presented with cranial nerve deficit at initial diagnosis. The location of the majority of rhabdomyosarcomas was orbital (N = 9; 32.1%), followed by parapharyngeal (n = 4; 14.2%) and sinonasal (n = 3; 10.7%). All patients (n = 28; 100%) received polychemotherapy, additional adjuvant radiation therapy was carried out in 24 patients (85.7%), and surgery was performed in 12 cases (42.9%). The 5-year overall survival was 91.3%, and median progression-free survival was 46 ± 67.4 months. Common side effects resulting from chemotherapy and radiation therapy included neutropenia, mucositis, nausea and vomiting, and radiodermatitis, long-term side effects included microsomia and facial mutilation. Conclusion  Multimodality treatment of rhabdomyosarcomas of the head and neck in pediatric patients may lead to a 5-year overall survival of up to 91.3%. Keywords  Rhabdomyosarcoma · Alveolar · Embryonal · Head and neck

Introduction Rhabdomyosarcoma (RMS) is a highly malignant soft tissue tumor derived from embryonic primitive mesenchyme that differentiates into striated skeletal muscle and is a rare differential diagnosis in tumors of the head and neck. * Sophia Marie Häußler sophia‑[email protected] 1

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Department of Otorhinolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Virchow‑Klinikum, Augustenbuger Platz 1, 13353 Berlin, Germany Department of Radiation Oncology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Virchow‑Klinikum, Berlin, Germany

In pediatric patients, RMS accounts for 4.5–7% of all malignant tumors and for 40–50% of all soft tissue sarcomas (Radzikowska et al. 2016; Ma et al. 2015). The predilection site of RMS in patients younger than 15 years is the head and neck region in 35–40% of all cases (Reilly et al. 2015), whereas in adults, < 1% of RMS are localized 3



Department of Otorhinolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Charité Mitte, Berlin, Germany

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Department of Pediatrics, Division of Oncology and Hematology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Virchow‑Klinikum, Berlin, Germany

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Department of Otorhinolaryngology, Head and Neck Surgery and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

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in the head and neck area (Wurm et al. 2005). The incidence in pediatric patients (< 15 years of age) in Germany between 2005 and 2014 was 5.2 in 1,000,000 patients, the highest incidence was seen in patients aged between 1 and 4 years (Hess et al. 1998; Orbach et al. 2017; McCarville et al. 2001). Most RMS cases result from sporadic mutations, whereas there are cases that are associated with Beckwith–Wiedemann syndrome, Li–Fraumeni syndrome, Noonan syndrome or cardiofaciocutaneous syndrome (Radzikowska et al. 2016). There are four different histological subentities of RMS: embryonal, alveolar, anaplastic, and mixed-type RMS. The embryonal subtype is the most common in children (60%) and comprises the botryoid and spindle cell subtypes. Alveolar RMS accounts for approximately 20% of RMS in children (Radzikowska et al. 2016; McCarville et al. 2001). Anaplastic RMS is also called pleomorphic RMS and is most commonly seen in adults. RMS of the head and neck are classified in parameningeal, nonparameningeal and nonparameningeal orbital localization. Parameningeal localization includes paranasal sinuses, nasal cavity, nasopharynx, skull base area, mastoid process as well as infratemporal and pterygopalatine fossa, and the middle ear. Due to their localization parameningeal RMS are likely to infiltrate central nervous tissue. They show a tendency to grow unnoticed and are often asymptomatic in early tumor stages. Nonparameningeal localizations account for 9–16% of patients with localized RMS (Orbach et al. 2017) and include all other head and neck regions as well as the orbit. Symptoms include swelling in the head and neck region, purulent or bloody secretion, dysphagia, exophthalmos, eye ball immobilization, strabismus or periorbital ecchymosis (Radzikowska et al. 2015). The aim of our study was to fill an epidemiological gap and evaluate the outcome of juvenile head and neck RMS with regard to different subtypes and therapy regimens over the last 20 years at one of the largest tertiary referral centers in Europe.

Materials and methods Following institutional review board approval (appl. no.: EA2/153/15), we performed an ICD-10 based study on rhabdomyosarcoma (C 49.0-; C69.0-) at the Charité, Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, database system SAP (SAP Deutschland SE & Co. KG, Walldorf, Germany) containing patients’

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records over a 20-year period (05/1996–06/2016) to identify histologically confirmed cases of RMS of the head and neck in children. Furthermore, data from patients’ health records and the German Childhood Cancer Registry have been investigated. RMS is staged by the TNM system and/or IRS classification. The TNM system differentiates T = Tumor [T1: tumor limited to anatomic site of origin; T2: tumor extends away from site of origin (a ≤ 5 cm; b ≥ 5 cm)], N = Nodes (N0: no tumor in lymph nodes; N1: lymph nodes with tumor), M = Metastases (M0: no distant metastases; M1: distant metastases). The current version of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) TNM staging system for soft tissue sarcoma of the head and neck (AJCC 2017) excludes embryonal and alveolar rhabdomyosarcoma. The IRS classification includes four stages: stage 1 includes tumors of the orbit or nonparameningeal tumors; stage 2 describes a local tumor < 5 cm, non-orbital, parameningeal, N0; stage 3 comprises tumors not included in stage 1, > 5 cm, N0 or N1; stage 4 describes a tumor with distant metastases. The treatment of head and neck RMS in patients younger than 21 years of age at our institution follows the current protocols and guidelines of the Cooperative Soft Tissue Sarcoma Studies, which were adapted following the study results in regard to risk stratification and survival [Cooperative Weichteilsarkom Studie CWS-81 (Koscielniak et al. 1992), CWS-86 (Koscielniak et al. 1994), CWS-91 (Dantonello et al. 2009), CWS-96, CWS-2002-P, CWS2007-HR]. The risk stratification for each patient group follows the CWS-2002-P study and is displayed in Table 1. Chemotherapy regimens were applied according to the current protocol and the risk group: In the CWS-96 trial: standard risk group IVA (Ifosfamide, Vincristine, Actinomycin-D); high risk group: VAIA (Vincristine, Actinomycin-D, Ifosfamide, Adriamycin) or CEVAIE (Carboplatin, Epirubicin, Vincristine, Actinomycin-D, Ifosfamide). In the CWS-2002P trial: standard risk group IVA, high risk group: VAIA and in some cases maintenance chemotherapy with Cyclophosphamide, Vinblastine, Etoposide. In the CWS2007 HR trial the high risk group was randomized in an arm with maintenance chemotherapy (Trofosfamide, Etoposide, Idarubicine) and an arm with no maintenance chemotherapy. Chemotherapy was conducted either neoadjuvant and adjuvant or adjuvant after local treatment by radiation therapy or surgery. Patients’ baseline characteristics (age on diagnosis, sex, tumor location, stage, and histology) were obtained (Table 2) as well as the clinical presentation and side effects from

Journal of Cancer Research and Clinical Oncology Table 1  Risk stratification for RMS of the head and neck in children according to the CWS2002P protocol

Risk

Histology

Location

Nodes

Surgical resection

Tumor size (cm); patients age (years)

Low Intermediate

Embryonal Embryonal Embryonal Embryonal Embryonal Embryonal Alveolar Alveolar

All All Orbital/ nonparameningeal Parameningeal Orbital/ nonparameningeal All All All

N0 N0 N0 N0 N0 N1 N0 N1

R0 R0 R1, R2 R1, R2 R1, R2 R1, R2 R0, R1, R2 R1, R2

≤ 5; ≤ 10 ≥ 5; ≥ 10 All ≤ 5; ≤ 10 ≥ 5; ≥ 10 All All All

High

very high

Table 2  Patients and tumor baseline characteristics Characteristics

n

%

Patients  Male  Female Mean patient age at diagnosis Histological subtype  Embryonal  Alveolar  Unknown IRS stage  1  2  3  4  Unknown Tumor (T)  T1  T2  Tx Nodes (N)  N0  N1  Nx Metastases (M)  M0  M1  Mx Localisation  Nonparameningeal  Parameningeal

28 17 11 6.8 ± 5.0

100 60.7 39.3

24 3 1

85.7 10.7 3.6

5 4 14 3 2

17.9 14.3 50 10.7 7.1

4 22 2

14.3 78.6 7.1

23 2 3

82.2 7.1 10.7

23 3 2

82.2 10.7 7.1

14 14

50.0 50.0

therapy. Overall survival rates and progression-free survival were calculated using the Kaplan–Meier method. Univariate regression analysis was performed using the log-rank test.

Table 3  Tumor location of head and neck rhabdomyosarcomas

Tumor location

n %

Orbital Parapharyngeal Paranasal sinuses Nasopharynx Petrosal bone Temporal fossa Nose Auditory canal Pterygopalatine fossa Skull base Soft palate Cheek

9 32.1 4 14.2 3 10.7 2 7.1 2 7.1 2 7.1 1 3.6 1 3.6 1 3.6 1 3.6 1 3.6 1 3.6

Statistical analysis used SPSS software (v21; IBM SPSS Statistics, Chicago, IL, USA). Significance was set at a level of p ≤ 0.05.

Results Twenty-eight patients were identified, of which 17 (60.7%) were male and 11 (39.3%) were female patients. The mean age at diagnosis of RMS was 6.8 ± 5.0 years (range 0.1–16.0 years). Nine patients (32.1%) presented with cranial nerve deficit at initial diagnosis including vision impairment by optic neuropathy (n = 6) and dysphagia by glossopharyngeal and vagus nerve deficit (n = 2). Fourteen patients (50%) presented with painless swelling, two patients (7.1%) experienced bleeding, and two patients (7.1%) had recurrent infections on tumor site. The histological subtype in most cases was embryonal (n = 24; 85.7%), followed by alveolar subtype (n = 3; 10.7%). One patient presented with unknown histological subtype (3.6%), anaplastic or mixed-type RMS was not seen in our cohort.

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Five patients (17.9%) had an IRS stage 1; four patients (14.3%) stage 2; 14 patients (50%) stage 3; three patients (10.7%) were diagnosed with stage 4 tumors and 2 patients (7.1%) could not be assigned an IRS stage. TNM classification distributions are listed in Table 2. The majority of RMS were in an orbital location (N = 9; 32.1%), followed by parapharyngeal (n = 4; 14.3%) and sinonasal (n = 3; 10.7%). Detailed tumor site distributions are given in Table 3. Treatment of head and neck RMS in children was carried out according to the CWS protocols and guidelines (Table 4). All patients (n = 28; 100%) received a polychemotherapy; 21 patients (75%) received IVA (Vincristine, Ifosfamide and Actinomycin-D), seven patients (25%) received VAIA (Vincristine, Ifosfamide, Actinomycin-D and Adriamycin). In eight patients (28.6%), maintenance chemotherapy was administered (Table 4). Adjuvant radiation therapy was carried out in 24 patients (85.7%), from which 10 (35.7%) had undergone previous surgical resection of the tumor. There were 10 cases (35.7%) with conventional radiation therapy, four cases (14.3%) with 3DCRT (3D conformal radiation therapy), three cases (10.7%) with proton beam therapy, and two cases (7.1%) with intensity modulated radiation therapy. Radiation Table 4  Therapy of rhabdomyosarcomas according to the CWS protocols and guidelines Therapy Polychemotherapy  Total  Vincristin, Ifosfamid, Actinomycin-D  Vincristin, Ifosfamid, Actinomycin-D  Adriamycin Maintenance chemotherapy  Total  Cyclophosphamid, Vincristin  Cyclophosphamid, Vinblastin  Trofosfamid, Etoposid, Idarubicin  Carboplatin, Epirubicin, Vincristin  Adjuvant radiation therapy Total  Conventional radiation therapy  3DCRT  Proton beam therapy  IMRT  Radiation in another hospital Surgery (resection status)  Total  Clear margins (R0)  Involved on histology (R1)  Involved macroscopically (R2)

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n

%

28 21 7

100 75.0 25.0

8 3 2 2 1

28.6 10.7 7.1 7.1 3.6

24 10 4 3 2 5

85.7 35.7 14.3 10.7 7.2 17.9

12 0 10 2

42.9 0 35.7 7.1

therapy was conducted on another five patients (17.9%) in different hospital. Initial surgery was performed in 12 cases (42.9%) with no clear resection margins on histopathological examination (“R1”) (Table 4). Three patients (10.7%) died due to tumor progression during a mean follow-up time of 56.2 months (4.7 years), two had a RMS with parameningeal growth, one had a RMS with nonparameningeal localisation. We included 26 patients (92.9%) in the survival analysis; two patients were excluded because they did not receive treatment at our hospital and thus were lost to follow-up after the first consultation. The 5-year overall survival (OS) rate was 91.3%. The estimated mean overall survival for the RMS patients in this study was 211 months after diagnosis. Median overall survival data could not be calculated as there were only three events (death). In regression analysis comparing the overall survival (OS) of patients of age 0–10 and 10–18 years, there was no significant difference (p = 0.079, Fig. 1a). There was also no significant difference when comparing OS in female versus male patients (p = 0.242, Fig. 1b). When comparing nonparameningeal to parameningeal RMS, no significant difference in OS was seen (p = 0.637, Fig. 1c). Median progression-free survival (PFS) was 46.0 ± 67.4 months (range 8–251 months, Fig. 2b). Seven patients (25.0%) experienced a local recurrence after a median time of 14.5 months (range 8–40 months), which was treated with radiation therapy (n = 2), with radiation and polychemotherapy (n = 2), with polychemotherapy (n = 2), or with surgery and adjuvant irradiation (n = 1) (Figs. 3, 4). Common side effects resulting from chemotherapy and radiation therapy included neutropenia, mucositis, nausea and vomiting, and radiodermatitis. There was one patient (3.6%) with secondary malignancy, which was a radiationinduced sarcoma NOS (not otherwise specified) of the right pterygopalatine fossa treated with Ifosfamide, Topotecan and Cyclophosphamide (Table 5).

Discussion Sarcoma, and especially RMS, is a rare differential diagnosis in tumors of the head and neck and so far only a few case series have been reported (Radzikowska et al. 2016; Vasiwala et al. 2015; Chirat et al. 2016; Brookes and van Velzen 1990; Blatt et al. 1997; Schouwenberg et al. 1998; Mazeron et al. 2014) with combined 56 patients and three reviews (Orbach et al. 2017; Leaphart and Rodeberg 2007; Zevallos et al. 2010) have described clinical presentation,

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Fig. 1  Kaplan–Meier curve of overall survival probability of patients with RMS. a 0–10-years-old patients versus 11–18-years-old patients (p = 0.079). b Female versus male patients (p = 0.242). c Nonparame-

ningeal versus parameningeal RMS (p = 0.637). d IRS Stage 1–2 versus IRS Stage 3–4 (no statistic was calculated because all cases IRS stage 1–2 are censored)

Fig. 2  Kaplan–Meier curve of overall survival probability of children with head and neck RMS (a) and progression-free survival (b)

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Fig. 3  MRI images of a 3-yearold female patient with RMS of the left auditory canal and middle ear (the star marks the tumor). Images a (T2 tse) and b (T2 Drive) show the tumor before treatment. Images c (T1) and d (T2) show images 5 years after initial diagnosis and 15 months after radiation therapy of local recurrent RMS, the images show complete remission

treatment and clinical outcome of young patients with RMS of the head and neck. Fifty percent of our patients presented with painless swelling in head and neck region, the histological subtype in most cases was embryonal (85.7%), and the majority of RMS was located in the orbit (32.1%). The treatment regimens according to the CWS protocols and risk stratifications only differed slightly in our cohort. All patients (n = 28) received polychemotherapy and adjuvant radiation therapy was carried out in 24 patients (85.7%). Initial surgery was performed in 12 cases (42.9%) with no clear resection margins on histopathological examination (“R1”). The 5-year overall survival (OS) rate was 91.3%. The estimated mean overall survival for the RMS patients in our study was 211 months after diagnosis. Median progression-free survival (PFS) was 46.0 ± 67.4 months (range 8–251 months). Early symptoms of head and neck RMS include painless swelling, facial pain, dysphagia, nasal congestion and

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recurrent infections, which can be mistaken as benign conditions or might even be overlooked (Reilly et al. 2015; Sturgis and Potter 2003; Radzikowska et al. 2015). Cranial nerve deficit should always be a warning sign for the differential diagnosis of a malignant tumor (Reilly et al. 2015). Patients with RMS of the middle ear or auditory canal may present with ear pain, recurrent infections, aural polyp or facial nerve palsy (Sturgis and Potter 2003; Radzikowska et al. 2015; Vasiwala et al. 2015; Chirat et al. 2016; Jaffe et al. 1971). One of our patients with an embryonal RMS presented with bleeding from the auditory canal (Fig. 2). In all cases of RMS a tumor biopsy was performed to confirm the histopathological diagnosis. Radiological imaging was performed before tumor biopsy, which included magnetic resonance imaging (MRI) with i.v. contrast to detect the location and extent of the tumor, as well as a computed tomography (CT) scan with i.v. contrast to show bone infiltration or destruction (Zhu et al. 2014; Brookes and van Velzen 1990) as well as to detect metastases. For staging and

Journal of Cancer Research and Clinical Oncology

Fig. 4  Stereotactic plans (sequential boost) for a patient with RMS of the left auditory canal. a Initial stereotactic plan with 1.8  Gy single dose to a total dose of 41.4  Gy and b stereotactic boost plan with 5 × 1.8–9  Gy (total dose in planning target volume: 49.4  Gy)

are shown on representative axial, coronal and sagittal planning CTimages. Surrounding 95%-isodose of prescribed dose is shown in pink. Each plan was generated with 10 conformal beams

Table 5  Long-term side effects on radiation and chemotherapy of rhabdomyosarcoma

discussed studies were treated according to the Cooperative Soft Tissue Sarcoma Studies (Cooperative Weichteilsarkom Studie CWS-81 (Koscielniak et al. 1992), CWS86 (Koscielniak et al. 1994), CWS-91 (Dantonello et al. 2009), CWS-96, CWS-2002-P, CWS-2007-HR). Surgical resection remains the favored local treatment option especially in a multimodality approach combined with chemotherapy (Rodeberg et al. 2002). A residual tumor mass after surgery negatively influences overall survival. Surgical resection with clear margins may avoid additional radiation therapy and therefore prevent patients from longterm side effects of radiation therapy (Daya et al. 2000; Leaphart and Rodeberg 2007; Clement et al. 2016). On the other hand, the location and extent of RMS may limit the possibilities of surgery with regard to morbidity and mutilation. RMS of parameningeal areas such as the nasopharynx, temporal bone and paranasal sinuses are mostly not accessible to surgery and unlikely to be resected with clear margins and without mutilation (Daya et al. 2000). In external beam radiotherapy treatment techniques include 3DCRT, proton beam therapy and IMRT (intensity modulated radiotherapy). Other radiation therapy modalities include brachytherapy, which may be applied for orbital RMS (Schoot et al. 2016a, b), RMS of the external auditory canal (King et al. 2017) and for RMS of the nasolabial fold (Mazeron et al. 2014) in combination with ablative and later

Side effects

n

%

Total Radiation-induced sarcoma Renal insufficiency Hypopituitarism Microsomia Hypothyroidism Amaurosis Cataract Facial asymmetry Hemiparesis Myelodysplastic syndrome

14 1 1 2 2 1 2 1 1 2 1

100 7.1 7.1 14.3 14.3 7.1 14.3 7.1 7.1 14.3 7.1

detecting distant metastases ultrasound and PET/CT have been carried out. In a recent study, Norman et al. (2015) discuss PET/CT as a radiological imaging instrument that may increase the accuracy of initial staging and detection of lymph node and distant metastases in pediatric RMS. Federico et al. (2013) also recommended PET/CT for staging of pediatric RMS, especially to identify lymph node, bone, and bone marrow as well as soft tissue metastases. The therapy of RMS of the head and neck is a multimodality treatment that in most cases combines polychemotherapy, radiotherapy and surgery. Most patients in the

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reconstructive surgery following chemotherapy for residual disease (Schouwenburg et al. 1998). Long-term side effects of radiation therapy included radiation-induced sarcoma of the pterygopalatine fossa, hypopituitarism, microsomia, hypothyroidism, facial asymmetry, hemiparesis, myelodysplastic syndrome, amaurosis and cataract. Secondary malignant neoplasms occur particularly after combining alkylating chemotherapy combined with radiotherapy (Heyn et al. 1993; Scaradavou et al. 1995); Heyn et al. (1993) reported that the most common secondary malignancy was bone sarcoma followed by acute nonlymphoblastic leukemia (ANLL) with a 10-year cumulative incidence rate of 1.7%. The most frequent late complications after treatment of soft tissue sarcomas of the head and neck include growth retardation, hypoplasia or facial asymmetry, malformed teeth, vision impairment, and sensorineural hearing loss (Raney et al. 1999; Schoot et al. 2016a, b). Within our cohort, three patients (10.7%) died due to tumor progression during a mean follow-up time of 56.2 months (4.7 years), two had a RMS in parameningeal localization, and one had a RMS in nonparameningeal localisation. In this retrospective study an excellent 5-year overall survival of 91.3% was achieved for pediatric RMS patients although this finding needs to be regarded with caution due to the high proportion of embryonal compared to alveolar RMS (85.7 vs. 10.7%) and due to the limited number of patients compared to other studies. Radzikowska et  al. (2016) treated 20 children (70% embryonal RMS, 30% alveolar RMS) with head and neck RMS by primary surgical resection. In that group the 5-year overall survival was estimated to be 50%. In a SEER review, Perez et al. (2011) reported on a 5-year overall survival of 60% for 1544 patients < 20 years with RMS at any location (67% embryonal RMS, 32% alveolar RMS). Raney et al. (1999) reported a 5-year overall survival of 73% in patients with local parameningeal sarcoma. In another SEER review Turner and Richmon (2011) reported that the 5-year overall survival of patients with head and neck RMS (N = 558) was statistically unchanged during a study period of 30 years with a relative overall survival of 62.8%. In contrast, Simon et al. (2002), who reported on a 5-year overall survival of 60% in head and neck RMS (N = 49), and Zevallos et al. (2010), who saw a 5-year overall survival of 66.8% in pediatric parameningeal sarcomas (N = 34) as well as the IRS group, indicate an improvement in outcome with multimodality treatment during the recent years. In a SEER review which included 286 patients with sinonasal RMS, Unsal et al. (2017) reported that this form of RMS had the poorest prognosis of parameningeal head and neck RMS with a 5-year overall survival of 35.1%; surgery was the treatment with the best outcome in this particular

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subentity, sinonasal RMS are indicated to have the poorest prognosis of parameningeal head and neck RMS with a 5-year overall survival of 35.1%; surgery was the treatment with the best outcome in this particular subentity. Favourable prognostic factors for patient outcome are: age at diagnosis < 10 years, maximum tumor extent < 5 cm, embryonal histology and localized disease (Perez et al. 2011; Raney et al. 2002; Turner and Richmon 2011; Simon et al. 2002; Zevallos et al. 2010; Unsal et al. 2017). In this study, patient age at diagnosis was < 10 years in 19 patients (67.9%), 85.7% (N = 24) of the cases were embryonal RMS and 82.1% (N = 23) of the cases were localized disease with no lymph node or distant metastases; this may explain the excellent 5-year overall survival of 91.3%.

Conclusion RMS of the head and neck is a rare differential diagnosis in head and neck tumors and may present with painless swelling, bloody secretion, dysphagia, exophthalmos, and vision impairment. In this study, the multimodality treatment with an adjusted combination of chemotherapy, radiation therapy, and surgery resulted in a 5-year overall survival of 91.3%, but there may be a certain risk of long-term effects such as facial asymmetry and microsomia due to radiation therapy.

Compliance with ethical standards  Funding  This study has not received any funding. Conflict of interest  The authors declare that they have no conflict of interest. Ethical approval and informed consent  All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and of the 1964 Helsinki declaration and its later amendments. Informed consent was obtained from all patients.

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